Engineering Crystals Using sp3-C Centred Tetrel Bonding Interactions

Article abstract of DOI:10.1002/chem.202002613

1,1,2,2-Tetracyanocyclopropane derivatives 1 and 2 were designed and synthesized to probe the utility of sp³-C centred tetrel bonding interactions in crystal engineering. The crystal packing of 1 and 2 and their 1,4-dioxane cocrystals is dominated by sp³-C(CN)₂???O interactions, has significant C???O van der Waals overlap (≤0.266 ?) and DFT calculations indicate interaction energies of up to ?11.0 kcal mol^?1. A cocrystal of 2 with 1,4-thioxane reveals that the cyclopropane synthon prefers interacting with O over S. Computational analyses revealed that the electropositive C₂(CN)₄ pocket in 1 and 2 can be seen as a strongly directional ‘tetrel-bond donor’, similar to halogen bond or hydrogen bond donors. This disclosure is expected to have implications for the utility of such ‘tetrel bond donors’ in molecular disciplines such as crystal engineering, supramolecular chemistry, molecular recognition and medicinal chemistry.

Full text of DOI:10.1002/chem.202002613

Accepted Article
Accepted Article
Title: Engineering crystals using sp3–C centred tetrel bonding
interactions
Authors: Tiddo Jonathan Mooibroek, Julius J. Roeleveld, Siebe J.
Lekanne Deprez, Abraham Verhoofstad, Antonio Frontera,
and Jarl Ivar van der Vlugt
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202002613
Link to VoR: https://doi.org/10.1002/chem.202002613
01/2020

10.1002/chem.202002613
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Engineering crystals using sp3–C centred tetrel bonding
interactions
Julius J. Roeleveld,[a] Siebe J. Lekanne Deprez,[a] Abraham Verhoofstad,[a] Antonio Frontera,[b] Jarl Ivar
van der Vlugt,[a, c] and Tiddo Jonathan Mooibroek*[a]
[a]
J. J. Roeleveld, S. J. Lekanne Deprez, A. Verhoofstad, Dr. Ir. J. I. van der Vlugt and Dr. T. J. Mooibroek
van ‘t Hoff Institute for Molecular Sciences
Universiteit van Amsterdam
Science Park 904, 1098 XH Amsterdam, The Netherlands
E-mail: t.j.mooibroek@uva.nl
[b]
[c]
Prof. Dr. A. Frontera
Department of Chemistry
Universitat de les Illes Balears
Crts de Valldemossa km 7.6, 07122 Palma de Mallorca (Baleares), Spain
Prof. Dr. Ir. J. I. van der Vlugt
Institute of Chemistry
Carl von Ossietzky University Oldenburg
Carl-von-Ossietzky-Straße 9-11, D-26219 Oldenburg, Germany
Supporting information for this article is given via a link at the end of the document.
Abstract: 1,1,2,2-Tetracyanocyclopropane derivatives 1 and 2 were
designed and synthesized to probe the utility of sp3-C centred tetrel
bonding interactions in crystal engineering. The crystal packing of 1
and 2 and their 1,4-dioxane cocrystals is dominated by sp3-C(CN)2∙∙∙O
interactions with significant van der Waals overlap (≤ 0.266 Å) and
DFT calculations indicate interaction energies of up to –11.0 kcal·mol-
1. A cocrystal of 2 with 1,4-thioxane reveals that the cyclopropane
synthon prefers O-binding over S-binding. Computational analyses
revealed that the electropositive C2(CN)4 pocket in 1 and 2 can be
seen as a strongly directional ‘tetrel-bond donor’, similar to halogen
bond or hydrogen bond donors. This disclosure is expected to have
implications for the utility of such ‘tetrel bond donors’ in molecular
disciplines such as crystal engineering, supramolecular chemistry,
molecular recognition and medicinal chemistry.
importance to life. Carbon-centred interactions with carbonyls are
well established,[11] and interactions between (coordinated)
acetonitrile,[12] carbon monoxide[13] and carbon dioxide[14] with
appropriate acceptors have also been reported. However, these
involve sp2- or sp-hybridized carbon atoms that do not align with
the definition of a σ-hole interaction (but rather some type of π–
interaction). Interestingly, polar interactions with sp3-hybridized
carbon atoms can persist with methyl groups in crystal
structures.[15] Moreover, bonding interactions with sp3 carbon are
10c]
implicated in the ‘advent’ complex[4b,
of canonical SN2
nucleophilic displacement reactions, such as [Cl–···CH3I]– upon
the attack of Cl– on iodomethane.[4b, 16] In analogy to the halogen,
chalcogen and pnictogen bonding nomenclature,[17] such
interactions can be termed a ‘tetrel bonding interaction.’[18]
A supramolecular synthon that would allow for predictable
and directional sp3-C centered tetrel bonding interactions has not
been experimentally established to date. Aided by computational
insights, we predicted that the sp3 hybridized C(CN)2 centers[19]
present in 1,1,2,2-tetracyanocyclopropane (TCCP) could be a
suitable sterically accessible σ–hole.[20] We recently reported that
the sp3-carbon tetrel bonding potential of dimethyl-TCCP allows
for supramolecular adduct formation with the electron-rich O-atom
of tetrahydrofuran, both in the solid state and in the gas phase.[21]
Introduction
Phenomena such as host-guest complexation, molecular
aggregation, crystallization and protein folding are often largely
driven by non-covalent interactions.[1] Such interactions include
hydrogen and halogen bonding,[1a, 2] which have recently been
contextualized as examples of so-called ‘σ-hole interactions’.[3]
A
σ-hole can be seen as region of electropositive potential along the
vector of a covalent bond. The location of this potential coincides
with the σ* orbital of that bond. The ultimate conclusion of a strong
σ-hole donor-acceptor interaction can be the breaking and/or
making of a σ bond, such as in the reaction of I2 with I– to form
[I3]–.[4] In principle, each non-metallic element of the periodic table
could be involved in σ-hole interactions, provided the atom is
placed in the appropriate molecular framework. For example:
sulfur[5] atoms in dithienothiophenes[6] have been utilised as σ-
hole donors in catalysis,[7] to realise anion transport over
membranes,[8] and as a design element in mechanosensitive
fluorescent probes.[9]
Here, we exploit and extend on this principle by demonstrating
crystal engineering with sp3–C tetrel bonding interactions using
TCCP derivatives 1 and 2 (Figure 1).
Figure 1. Molecular structures of 1 and 2, together with a Molecular Electrostatic
Potential map (MEP) of 2 and 1,4-dioxane calculated at the DFT/B3LYP-
D3/def2-TZVP level of theory. The MEP is colour coded from electro-positive
(blue) to electronegative (red) and the indicated potentials are in in kcal·mol-1.
To date, a notable absentee among the non-metal elements
that have been rationally exploited as σ-hole donor is carbon,[10]
which is ubiquitously present in synthetic chemistry and of central
1
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Compound 1 is the bulkier ethyl-derivative of the previously
exploited dimethyl-TCCP. Cyclopropane 2 can be seen as a cyclic
ether analogue of 1, and was designed to combine a σ-hole donor
and acceptor within the same molecule. The Molecular
Electrostatic Potential map (MEP) of 2 shown in Figure 1 clearly
illustrates that the cyclopropane ring of 2 bears the large positive
potential (a sort of hybrid of two σ-holes) located on the sp3
C2(C≡N)2 atoms (the MEP of 1 is comparable). An interesting
feature is that the σ-hole is observed at the middle of the C–C
bond rather than two distinct σ-holes opposite to the C–C bonds
thus showing that the individual areas of depleted electron density
overlap and merge. [20a, 22] It is worth mentioning that this potential
is in-between the calculated potential on the H-atoms in water
(+55 kcal·mol-1) and ammonia (+35 kcal·mol-1) when computed at
the same level of theory.[21] The MEP of 1,4-dioxane shown in
Figure 1 illustrate the electronegative potential on the O-atoms of
cyclic ethers such as 2, which are thus anticipated to engage in
directional sp3-C···O interactions. Here we confirm this
hypothesis by disclosing the crystal structures of 1, 2,
[1···dioxane], [2···dioxane] and [2···thioxane] and show that their
packing is dominated by the anticipated sp3-C···O interactions.
The intramolecular distances and angles measured within these
structures (not shown) can be seen as normal.[27] The crystal
packing of 1 is organized by stacks of nitrile···nitrile interactions
(Figure S5b). However, geometry optimization of a [1···1] dimer
extracted from the crystal structure (ΔEBSSE = –4.8 kcal·mol-1)
converged in a rather different ordering that is more tightly packed
(ΔEBSSE = –7.8 kcal·mol-1, see Figure S5c). Also, the sp3-C···N
distance elongated from 3.178 Å in the crystal structure to 3.255
Å in the DFT calculation. As with 1, the atomic coordinates found
for 2 were accurately reproduced by DFT (Figure S6b). In stark
contrast with the packing obtained for 1, crystal packing of the unit
cell for species 2 (Figure 2c) displayed infinite 1-dimensional [2ꝏ]
rows that are formed by intermolecular sp3-C···O interactions (see
Figure S7 for the packing in the other two dimensions). The
observed intermolecular distances of 3.017(7) Å (O1···C3) and
3.027(7) Å (O1···C2) are up to 0.203 Å shorter than the combined
van der Waals radii of C (1.70 Å) and O (1.52 Å) and thus highly
12, 20a, 20b, 28]
indicative of a bonding interaction.[4b,
The atomic
coordinates of a [2···2] dimer extracted from the crystal structure
(ΔEBSSE = –10.2 kcal·mol-1) could be reproduced fairly accurately
with a DFT geometry optimization, which also gave a large
interaction energy of ΔEBSEE = –11.0 kcal·mol-1 (see Figure S6c).
Moreover, the intermolecular sp3-C···O distances were
reproduced and actually slightly shorter than observed (2.977 and
3.022 Å with DFT).
Results and Discussion
The crystal structures and DFT calculations of 1 and 2 thus
indicate that the intermolecular nitrile···nitrile interactions
observed in 1 can be significantly distorted by other weak crystal
packing forces, while the sp3-C···O interactions observed in 2 are
strong enough to persist in and direct the crystal packing. This
implies that sp3-C···O interactions can be used as a design
feature to engineer crystal structures. To further develop this idea,
crystals of 1 and 2 were grown from 1,4-dioxane (see ESI for
details). As envisioned, 1 co-crystallized with a dioxane molecule
to form the [1···dioxane] crystal structure adduct shown in Figure
3a (ΔEBSSE = –10.9 kcal·mol-1). The observed intermolecular sp3-
C···O distances are up to 0.242 Å shorter than the sum of the van
der Waals radii of C and O (C3···O2). This is very similar to the
distances observed in the crystal packing of 2 (Figure 2c).
TCCP derivatives 1 and 2 are both synthetically accessible in
moderate to decent yields (34 – 58%) using a straightforward
modified literature procedure (see experimental and ESI for full
details and characterization).[21] Single crystals suitable for X-ray
diffraction measurements (see experimental for details) were
obtained by slow evaporation of a solution of 1 or 2 in
dichloromethane. The atomic coordinates contained within the
unit cells are shown in Figure 2a and b for 1 and 2[23] respectively
(see ESI for full details). Optimization of 1 at the B3LYP[24]
-
D3[25]/def2-TZVP[26] level theory accurately reproduced the crystal
structure coordinates of 1 (Figure S5a).
Figure 3. a) Single crystal X-ray diffraction structure of [1···dioxane]. b)
structure overlay of [1···dioxane] observed in the crystal structure (carbon in
black with ΔEBSSE = –10.9 kcal·mol-1) versus the adduct calculated by DFT at
the B3LYP-D3/def2-TZVP level of theory (carbon in grey). The RMSD using
only the coordinates of 1 is 0.120 (shown), when using all 39 atoms this value
is 0.145. c) crystal packing of the [1···dioxane] adduct. Nitrogen = blue, oxygen
= red and hydrogen = white.
Figure 2. Single crystal X-ray diffraction structures of 1 (a) and 2 (b). c) infinite
1-dimensional pillars of 2 observed in the crystal structure, held together by
short sp3 C···O contacts as shown by the two perspective views. Only distances
involving the cyclopropane C-atoms are shown (green dotted lines). For more
illustrations of crystal packing and a comparison to DFT optimized geometries,
see Figures S5 – S8. Nitrogen = blue, oxygen = red and hydrogen = white.
2
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A
DFT geometry optimization of [1···dioxane] essentially
atom consistently points towards the C1/C3 face of 2 and an S-
atom is directed towards the C1/C2 side of another molecule of 2.
Two [2ꝏ] rows are about 0.2 Å further apart in the thioxane versus
the dioxane co-crystals and the rows are also shifted by about 0.6
Å with respect to each other (see Figure S10). As can be seen in
Figure 5c and d, the O∙∙∙2 and S∙∙∙2 constellations of [2·thioxane]
could be reproduced by DFT. The interaction of thioxane-O with
the C1/C3 side of 2 (Figure 5c) has an interaction energy of
ΔEBSSE = –9.26 kcal·mol-1, which is nearly identical to the energy
calculated for a similar constellation in [2···dioxane] (Figure 4c).
The interaction of thioxane-S with the C1/C2 side of 2 (Figure 5c)
is about 2.3 kcal·mol-1 less favourable (–6.92 kcal·mol-1).
reproduced the observed atomic constellation in the crystalline
state (Figure 3b). The intermolecular sp3-C···O distances
observed in the crystal structure were also preserved and the
interaction energy (ΔEBSSE) was computed at –10.46 kcal·mol-1;
nearly identical to the energy obtained for the [2···2] adduct. As is
shown in Figure 3c, the [1···dioxane] adducts are packed within
the crystal by weak nitrile···nitrile and C–H···O interactions.
Crystallization of 2 from 1,4-dioxane also resulted in the
formation of a co-crystal and the unit cell of [2···dioxane] shown
in Figure 4a again reveals short intermolecular sp3-C···O
distances (up to 0.261 Å van der Waals overlap for C3···O2).
Figure 4. a) Single crystal X-ray diffraction structure of [2···dioxane]; b)
Perspective view of an infinite 1D chain of 2. The chains are separated by the
rows of dioxane molecules shown; c) and d) are structure overlays of the
[2···dioxane] constellations observed in the crystal structure (carbon in black
with calculated ΔEBSSE) versus those calculated by DFT at the B3LYP-D3/def2-
TZVP level of theory (carbon in grey, see also Figure S8). Only intermolecular
distances involving the cyclopropane C-atoms are shown. Nitrogen = blue,
oxygen = red and hydrogen = white.
Figure 5. a) Single crystal X-ray diffraction structure of [2···thioxane]; b)
Perspective view of an infinite 1D chain of 2. The chains are separated by the
rows of thioxane molecules shown; c) and d) are structure overlays of the
[2···thioxane] constellations observed in the crystal structure (carbon in black
with calculated ΔEBSSE) versus those calculated by DFT at the B3LYP-D3/def2-
TZVP level of theory (carbon in grey). Only intermolecular distances involving
the cyclopropane C-atoms are shown. Distances in green indicate van der
Waals overlap, distances in red indicate van der Waals shells are not
overlapping. Nitrogen = blue, oxygen = red and hydrogen = white.
As was expected, infinite 1-dimensional [2ꝏ] rows are observed
in the crystal packing of [2···dioxane] (Figure 4b, with ΔEBSSE = –
10.79 kcal·mol-1 for a dimer) that are nearly identical to those seen
in the structure of pure 2 (see Figure S8). In [2···dioxane] however,
the [2ꝏ] stacks are spatially separated by bridging dioxane
molecules. As is shown in Figure 4c and d, the interactions of
dioxane with the C1/C3 and C1/C2 faces of 2 could be accurately
reproduced by DFT. The interaction energies are similar at ΔEBSSE
~ –9.0 kcal·mol-1, yet significantly smaller than calculated for
[1···dioxane] and [2···2] (about –11 kcal·mol-1). This can be
understood by the reduced steric hindrance of the four cyano
groups at the C2/C3 face versus the two CH2 fragments present
at the C1/C2 and C1/C3 sides.[29]
When 2 was allowed to crystallize from 1,4-thioxane,
[2·thioxane] co-crystals could be isolated and characterized by
single crystal X-ray diffraction. As can be seen in Figures 5a and
b, this structure is very similar to the dioxane co-crystal (see
Figures 4a and b). Again, infinite 1-dimensional [2ꝏ] rows are
observed within the packing (Figure 5b, with ΔEBSSE = –10.69
kcal·mol-1 for a dimer) that are nearly identical to those observed
in [2···dioxane] (see Figure S10, bottom). The rows are held
together by bridging thioxane molecules, where the thioxane O-
Other orientations of the thioxane S-atom near C1/C3 or near
C2/C3 all gave a much less stable adduct than for the dioxane
analogues (by about 2 kcal·mol-1, see Figure S11). This implies
that the sp3-C-atoms in 2 are more oxophillic than thiophillic.
It is interesting to note that the smaller O (rvdW = 1.52 Å) is
found at the sterically most accessible C1/C3 face of 2, while the
larger S (rvdW = 1.8 Å) is located near the sterically more crowded
C1/C2 face of 2 (see Figure S12 for representation of the sterics).
This implies that the orientation of the thioxane molecules in-
between the [2ꝏ] rows is driven by sp3-C···O interactions, and is
not directed by a packing that minimizes steric hindrance. This
observation further supports that the sp3-C-atoms in 2 are more
oxophilic than thiophilic.
The Hirshfeld surfaces of 1 and 2 in all crystal structures
were also computed using CrystalExplorer 17.5 and the relevant
interaction energies were estimated at the DFT/B3LYP/6-31G
level of theory (Figure S13).[30] These analyses also revealed that
the main interactions in the crystal packing involve the sp3-C(CN)2
atoms, with interaction energies generally in line with the ΔEBSSE
energy values mentioned above.
3
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To probe the physical nature of the observed sp3-C···O
interactions and to place them into context, several
supramolecular adducts of 1,4-dioxane were selected for
comparative computational scrutiny. Besides 1 as tetrel bond
donor, we selected BMe3 as a prototypical Lewis acid, Br2 as a
halogen bond donor and H2O as the prototypical hydrogen bond
donor. The molecular representations and interaction energies
adducts shown in Figure 6 and observed the anticipated[36]
C/B/Br/H···O BCPs (see Figure S14).
All these theoretical analyses thus point at the striking similarities
between the physical origins and magnitude of sp3-C centred
tetrel bonding interactions with TCCP derivatives and other
prototypical electropositive partners.
(ΔEBSSE) of the adducts that were optimized at the B3LYP[24]
-
D3[25]/def2-TZVP[26] level of theory are collected in Figure 6. Also
shown are the results of a non-covalent interaction analysis[31] and
a Morokuma-Ziegler inspired energy decomposition analysis
(bottom).[15b, 32]
Summary and concluding remarks
In summary, this work provides access to designed sp3-C centred
tetrel bond synthons through targeted synthesis of 1 and 2. These
systems were designed to direct their crystal packing by utilising
polar sp3-C∙∙∙O interactions. The cyclopropane synthon prefers to
interact with sp3 oxygen over sp3 sulfur, as evidenced by the
[2···thioxane] co-cystal. DFT calculations indicate interaction
energies of up to –11.0 kcal·mol-1.
A diverse range of
computational analyses show that the electropositive sp3-C2(CN)4
pockets in 1 and 2 can be seen as a strongly directional ‘tetrel-
bond donor’, similar to halogen bond- or hydrogen bond donors.
These results thus demonstrate that ‘non-covalent sp3-C centred
tetrel bonding interactions’ can be used to engineer structures in
the crystal state. This disclosure has implications for the potential
utility of tetrel bond donors such as 1 and 2 in molecular
disciplines such as crystal engineering, supramolecular chemistry,
molecular recognition and medicinal chemistry.
Figure 6. The ‘non-covalent interaction’ (NCI) analysis of geometry optimized
structures, together with the interaction energies (ΔEBSSE) and an energy
decomposition analysis of 1,4-dioxane forming: a) sp3 tetrel-bonding
interactions with cyclopropane 1; b) traditional Lewis acid/base interaction with
trimethylborane; c) halogen bonding interactions with molecular bromine; and
d) hydrogen bonding to water. Calculations were performed at the B3LYP-
D3/def2-TZVP level of theory. In the NCI plots red and yellow = steric repulsion,
green = dispersion and blue = electrostatic attraction. Carbon = grey, nitrogen
= blue, oxygen = red and hydrogen = white. E.I., O.I. and D.I. stand for,
respectively, electrostatic-, orbital-, and dispertion interactions.
Experimental Section
The interaction energy of [1···dioxane] is clearly most stabilizing
at –10.5 kcal∙mol-1. The Lewis acid adduct [Me3B···dioxane]
comes second with ΔEBSSE = –8.5 kcal∙mol-1, while the halogen
bond complex [Br2···dioxane] and the hydrogen-bonded water
adduct are least stable with ΔEBSSE ~ –7 kcal∙mol-1. The energy
decomposition analysis revealed that in all cases, the electrostatic
component dominates the interaction by contributing 46-58%. In
[1···dioxane] the dispersive interactions are the second largest
contributor at 35% and orbital interactions contribute least with
15%. These proportions between dispersion and orbital
interactions are the reverse in the other adducts. This can be
rationalized considering that energy contributions from dispersive
forces scale with contact area,[33] of which the [1···dioxane]
adduct has the most. The larger contact area (i.e. dispersion)
might also explain the increased stability calculated for
[1···dioxane]. Likewise, the electrostatic and orbital interactions
might well be enhanced in the adduct with 1 because the contact
is effectively established with two instead of one Lewis acidic
atom(s).
The NCI plots shown at the bottom of Figure 6 reveal that
the electrostatic attraction (blue) always involves a dioxane O-
atom and that the region of this attraction roughly coincides with
sp3-C∙∙∙O, Me3B∙∙∙O, Br–Br∙∙∙O or HO–H∙∙∙O bonding interactions.
Moreover, it is clear from these plots that the dispersive
interactions (yellow/green) are significant and decrease in the
order 1 > Me3B > Br2 ≈ H2O.
Although the significance of intermolecular bond critical
points (BCPs) in Bader’s atoms-in-molecules (AIM) analysis[34]
has been questioned,[35] we also performed an AIM analysis of the
Materials and methods: All commercially available chemicals were
purchased from Sigma-Aldrich and used without further purification.
Solvents were utilized as supplied. 1H-, 13C-, and 2D-NMR spectra were
acquired at 298 K on a Varian VNMR S500a. Chemical shifts (δ) are
reported in parts per million (p.p.m.). Residual solvent resonances were
used as internal reference for δ-values in H-, and 13C-NMR. The FT-IR
1
spectra were measured on a Shimadzu MIRacle 10 single reflection ATR
with an IRAffinity-1S Fourier transform infrared spectrophotometer. Field
desorption (FR+eiFi)) mass spectra were recorded on an Advion (T)LC-
MS expression LCMS mass spectrometer (with a TLC plate express and
isocratic pump).
X-ray intensities were measured on a Bruker D8 Quest Eco diffractometer
equipped with a Triumph monochromator (λ = 0.71073 Å) and a CMOS
Photon 50 detector at a temperature of 150(2) K. Intensity data were
integrated with the Bruker APEX2 software.[37] Absorption correction and
scaling was performed with SADABS.[38] The structures were solved using
intrinsic phasing with the program SHELXT.[37] Least-squares refinement
was performed with SHELXL-2013[39] against F2 of all reflections. Non-
hydrogen atoms were refined with anisotropic displacement parameters.
The H atoms were placed at calculated positions using the instructions
AFIX 13, AFIX 43 or AFIX 137 with isotropic displacement parameters
having values 1.2 or 1.5 times Ueq of the attached C atoms. CCDC
1990043-1990048 contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
The graphical rendering of the crystal structures has C, N, O and S atoms
represented as thermal ellipsoids drawn at 50% probability and hydrogen
atoms drawn as spheres with 0.15 Å radius.
DFT geometry optimization calculations were performed with Spartan
2016 at the B3LYP[24]-D3[25]/def2-TZVP[26] level of theory, which is known
to give accurate results at reasonable computational cost and a very low
4
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basis set superposition error (BSSE).[25-26] The molecular fragments were
under reflux for 30 minutes. To the brown solution, 50 mL of a 0.2 M
solution of an aqueous bromine (0.52 mL, 10 mmol) solution was added
using a dropping funnel. During the addition of bromine, a precipitate
formed. The mixture was stirred under reflux overnight, after which it was
cooled to laboratory temperature and filtrated using a Büchner funnel.
Vacuum drying of the solid gave 1.231 g (5.80 mmol, 58% yield) of a white
crystalline powder analyzed as 2. Crystals suitable for SC-XRD could be
grown by slow diffusion from dichloromethane, acetonitrile and from 1,4-
dioxane. Physical data (see Figure S3 and S4 for NMR and IR spectra
respectively): 1H NMR (500 MHz; DMSO-d6) δ = 3.82 (bs, 4H, OCH2CH2),
1.96 (bs, 4H, OCH2CH2) p.p.m.; 13C NMR (126 MHz; DMSO-d6) δ = 109.6
(CN), 63.7 (OCH2CH2), 43.3 (C(CN)2), 29.3 (OCH2CH2), 26.9 (C(CH2)2)
p.p.m.; FT-IR (neat, main peaks) ν = 2900-3000 (w, C–H stretch), 2255 (m,
C≡N stretch), 1422-1230 (w, C–H and C–C stretch/bends), 1092 (s, C–O
stretch), 1026, 1009, 984, 941, 841, 729 (m, various C–C and C–O rock
and stretch) cm-1; HRMS (FD): m/z found (calcd) for [C11H8N4O]+:
212.0702 (212.0698). SC-XRD (from dichloromethane) of C11H8N4O, Fw
= 212.21, colourless block, 0.186×0.152×0.111 mm, monoclinic, Pn (No:
7), a = 6.9636(10), b = 11.4508(15), c = 7.0277(10) Å, α = 90, β =
114.125(4), γ = 90 °, V = 511.43(12) ų, Z = 2, Dₓ = 1.378 g/cm³, μ = 0.095
manually oriented in
a suitable constellation before starting an
unconstrained geometry optimization. The Amsterdam Density Functional
(ADF)[32a] modelling suite at the B3LYP[24]-D3[25]/TZ2P[26] level of theory
(no frozen cores) was used to compute the reported BSSE corrected
energies (ΔEBSEE
, using the ‘ghost atoms’ option for counterpoise
correction) of the optimized structures as well as the adducts observed in
the crystal structures. ADF was likewise used to compute the energy
decomposition and ‘atoms in molecules’[34] analyses (using the default
ADF settings). Details of the Morokuma-Ziegler inspired energy
decomposition scheme used in the ADF-suite have been reported
elsewhere[32a, 32b] and the scheme has proven useful to evaluate hydrogen
bonding interactions.[15b, 32c] The NCI analysis was performed with AIMAII
(version 19.10.12, available at aim.tkgristmill.com) using the defaults
settings: surface cut-off = 0.5 a.u.; cut-off to remove covalent density =
0.05 a.u.; color isosurface range = ± 0.04 a.u.. CrystalExplorer 17.5
(https://crystalexplorer.scb.uwa.edu.au) was used to compute Hirshfeld
surfaces and estimate interaction energies in the crystal structures (see
Figure S14).[30]
Structure overlays of atomic coordinates were fitted with the pair fitting
function of PyMOL, by minimizing the Root Mean Square Deviation
(RMSD) between two (selected) sets of atomic coordinates.
mm⁻¹. 9428 Reflections were measured up to a resolution of (sin θ/λ)max =
0.84 Å⁻¹. 1809 Reflections were unique (Rint = 0.0672), of which 1464 were
observed [I>2σ(I)]. 146 Parameters were refined with 2 restraints. R1/wR2
[I>2σ(I)]: 0.0559/0.0986. R1/wR2 [all refl.]: 0.0811/0.1053. S = 1.077.
Residual electron density between 0.234 and -0.19 e/ų. CCDC 1990043.
SC-XRD (from acetonitrile) of C11H8N4O, Fw = 212.21, colourless block,
1.167×0.393×0.258 mm, monoclinic, Pn (No: 7), a = 6.9428(5), b =
11.4157(9), c = 7.0013(6) Å, α = 90, β = 114.155(2), γ = 90 °, V = 506.32(7)
ų, Z = 2, Dₓ = 1.392 g/cm³, μ = 0.096 mm⁻¹. 11811 Reflections were
measured up to a resolution of (sin θ/λ)max = 0.77 Å⁻¹. 2299 Reflections
were unique (Rint = 0.0375), of which 2214 were observed [I>2σ(I)]. 146
Parameters were refined with 2 restraints. R1/wR2 [I>2σ(I)]: 0.041/0.1012.
R1/wR2 [all refl.]: 0.0432/0.1024. S = 1.173. Residual electron density
between 0.242 and -0.177 e/ų. CCDC 1990046. SC-XRD (from 1,4-
dioxane) of C15H16N4O3, Fw = 300.32, colourless block, 0.335×0.3×0.224
mm, monoclinic, P21/c (No: 14), a = 13.1886(9), b = 6.9180(5), c =
17.5471(11) Å, α = 90, β = 110.051(2), γ = 90 °, V = 1503.94(18) ų, Z =
4, Dₓ = 1.326 g/cm³, μ = 0.095 mm⁻¹. 49100 Reflections were measured
up to a resolution of (sin θ/λ)max = 0.8 Å⁻¹. 3072 Reflections were unique
(Rint = 0.0302), of which 2769 were observed [I>2σ(I)]. 199 Parameters
were refined with 0 restraints. R1/wR2 [I>2σ(I)]: 0.0484/0.1381. R1/wR2
[all refl.]: 0.0539/0.142. S = 1.154. Residual electron density between
0.362 and -0.248 e/ų. CCDC 1990045. SC-XRD (from 1,4-thioxane) of
3,3-diethyl-1,1,2,2-tetracyanocyclopropane (1): A 500 mL round-bottom
was charged with, respectively, a magnetic stirrer, ethanol (60 mL),
malononitrile (5.9514 g, 90 mmol), NaOAc (0.7378 g, 9 mmol) and 3-
pentanone (3.2 mL, 30 mmol). The colorless solution was heated under
reflux for 30 minutes. To the brown solution, 150 mL of a 0.2 M solution of
an aqueous bromine (1.56 mL, 30 mmol) solution was added using a
dropping funnel. During the addition of bromine, a precipitate formed and
the mixture darkened. The mixture was stirred at room temperature
overnight. The dark brown mixture was vacuum filtered and thoroughly
washed first with water and then with ice-cold ethanol. The residue was
1.993 g (10.1 mmol, 34% yield) of a white crystalline powder analyzed as
1. Crystals suitable for SC-XRD could be grown by slow diffusion from
dichloromethane and from 1,4-dioxane. Physical data (see Figure S1 and
S2 for NMR and IR spectra respectively): 1H NMR (500 MHz; DMSO-d6) δ
= 1.85 (q, 3JH,H = 20 Hz, 4H, CH2), 1.12 (t, 3JH,H = 10 Hz, 6H, CH3) p.p.m.;
13C NMR (126 MHz; DMSO-d6) δ = 109.8 (CN), 48.0 (C(CN)2), 27.3
(C(Et)2), 22.8 (CH2), 8.6 (CH3) p.p.m.; FT-IR (neat, main peaks) ν = 2900-
3000 (w, C–H stretch), 2255 (m, C≡N stretch), 1470, 1456 (s, C–H
bending), 1123-948 (m, various C–C and C–H rock and stretch), 801, 727,
669 (s, C–C rock and stretch) cm-1; HRMS (FD): m/z found (calcd) for
[C11H10N4]+: 198.0830 (198.0905). SC-XRD (from dichloromethane) of
C15H16N4O2S, Fw = 316.38, colourless plate, 0.528×0.375×0.22 mm,
orthorhombic, Pnma (No: 62), a = 17.9218(14), b = 12.4693(10), c =
6.9617(5) Å, α = 90, β = 90, γ = 90 °, V = 1555.7(2) ų, Z = 4, Dₓ = 1.351
g/cm³, μ = 0.221 mm⁻¹. 50993 Reflections were measured up to a
C11H10N4, Fw = 198.23, colourless block, 0.711×0.334×0.321 mm,
monoclinic, P21/n (No: 14), a = 11.6118(7), b = 6.7528(4), c = 14.2042(8)
Å, α = 90, β = 104.184(2), γ = 90 °, V = 1079.83(11) ų, Z = 4, Dₓ = 1.219
g/cm³, μ = 0.078 mm⁻¹. 28447 Reflections were measured up to a
resolution of (sin θ/λ)max = 0.6 Å⁻¹. 3886 Reflections were unique (Rint
=
0.0452), of which 3346 were observed [I>2σ(I)]. 109 Parameters were
refined with 0 restraints. R1/wR2 [I>2σ(I)]: 0.0605/0.1358. R1/wR2 [all
refl.]: 0.0713/0.1415. S = 1.15. Residual electron density between 0.688
and -0.577 e/ų. CCDC 1990047.
resolution of (sin θ/λ)max = 0.6 Å⁻¹. 5208 Reflections were unique (Rint
=
0.0339), of which 4092 were observed [I>2σ(I)]. 138 Parameters were
refined with 0 restraints. R1/wR2 [I>2σ(I)]: 0.0482/0.1121. R1/wR2 [all
refl.]: 0.0683/0.1245. S = 1.048. Residual electron density between 0.431
and -0.223 e/ų. CCDC 1990048. SC-XRD (from 1,4-dioxane) of
C
15H18N4O2, Fw = 286.33, colourless block, 0.53×0.237×0.161 mm,
Acknowledgements
monoclinic, Cc (No: 9), a = 10.9559(6), b = 20.9754(12), c = 8.3074(4) Å,
α = 90, β = 125.563(2), γ = 90 °, V = 1552.99(15) ų, Z = 4, Dₓ = 1.225
g/cm³, μ = 0.084 mm⁻¹. 31827 Reflections were measured up to a
TJM thanks NWO (VIDI project 723.015.006) for funding and AF
gratefully acknowledges MICIU/AEI from Spain for financial
support (project number CTQ2017-85821-R, FEDER funds).
resolution of (sin θ/λ)max = 0.84 Å⁻¹. 2726 Reflections were unique (Rint
=
0.0579), of which 2459 were observed [I>2σ(I)]. 193 Parameters were
refined with 2 restraints. R1/wR2 [I>2σ(I)]: 0.0446/0.0977. R1/wR2 [all
refl.]: 0.0536/0.1014. S = 1.149. Residual electron density between 0.175
and -0.185 e/ų. CCDC 1990044.
Keywords: sp3-C tetrel bonding interactions • supramolecular
chemistry • crystal engineering • density functional calculations •
small ring systems
6-oxa-1,1,2,2-tetracyanospiro[2.5]octane (2): A 100 mL round-bottom
was charged with, respectively, a magnetic stirrer, ethanol (20 mL),
malononitrile (1.6606 g, 30 mmol) and NaOAc (0.2459 g, 3 mmol). Upon
addition of tetrahydro-4H-pyran-4-one (0.93 mL, 10 mmol), a white
precipitate was formed, which dissolved when the mixture was heated
5
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10.1002/chem.202002613
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6
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10.1002/chem.202002613
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FULL PAPER
Entry for the Table of Contents
For the first time, it was shown that polar sp3-C centred tetrel bonding interactions can be used as a predictive tool to engineered crystal
structures. Observed sp3-C···O distances display up to 0.27 Å van der Waals overlap. Calculations using density functional theory
revealed interaction energies up to –11 kcal·mol-1.
7
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